The cytochromes P-450 are central to the metabolism of xenobiotics and drugs and to the activation and detoxification of carcinogens. Whether a potentially carcinogenic molecule is metabolized to an active carcinogen or to an excretable form may depend on the activity and substrate specificity of the forms of the P-450s which predominate in the target tissue. As a result of this, susceptibility to cancer induction may well depend on the regulation of expression of the genes for specific cytochromes P-450. We are using recombinant DNA techniques and other molecular biological methodologies to study the structure and the regulation of the genes for the P-450s. We have constructed cDNA clones complementary to methylcholanthrene(MC)-induced P-450 mRNA. We have used these clones to quantitate MC-P-450 mRNA levels in control and MC-induced rat liver and to isolate a complete, native MC-P-450 gene. The structure of this gene is now being analyzed and the regulatory regions of this gene will be identified and characterized both structurally and functionally. This gene will also be used to isolate related P-450 genes.